Abstract:

DESCRIPTION (provided by applicant): Malaria causes an estimated 500 million clinical cases and up to 2.7 million deaths annually, is responsible for a loss of greater than 1% of GDP in Africa annually, and is a serious concern for travelers and military personnel. Sanaria's long term goal is to develop and commercialize an attenuated Plasmodium falciparum sporozoite vaccine. In limited trials, this type of immunization has been shown to protect greater than 90% of human volunteers against experimental P. falciparum challenge, protect for greater than 10 months after last immunization, and protect against heterologous challenge. No other experimental malaria vaccine under development has been shown to approach these performance characteristics. Heretofore it has been considered impractical to develop such a vaccine, because volunteers have been immunized by the bite of infected mosquitoes. However, all findings in humans with irradiated sporozoites have been anticipated by studies in mice with rodent malaria, and there are data indicating that alternative immunization methods are feasible. In this project the rodent malaria parasite, P. yoelii will be used to demonstrate in mice that effective immunization can be accomplished using sporozoites that are removed from the mosquito and are not delivered intravenously (IV), and are cryopreserved. This will be done in 4 steps: 1) Establish a non-IV method of infecting mice with freshly dissected P. yoelii sporozoites; 2) Establish a non-IV method of immunizing mice with freshly dissected irradiated sporozoites that provides protection comparable to that achieved by the standard intravenous regimen; 3) Establish a method of cryo-preservation of sporozoites that retains viability, and demonstrate that such cryopreserved P. yoelii sporozoites are infectious when administered by a non-IV route; 4) Demonstrate that a non-IV method of delivery of attenuated, cryopreserved P. yoelii sporozoites can provide protection comparable to that achieved by the IV regimen. In addition, work will be conducted to demonstrate that efficient, cost-effective production of sporozoites that meet potential FDA standards of characterization, purity, potency, and safety is feasible, and that a practical, in vitro lot release assay for potency of the irradiated sporozoite vaccine is feasible.